Multiple Myeloma Clinical Trial Shows Distinct Survival Benefit with Lower Dose of Steroids

Monday, December 10, 2007

ATLANTA — Results of Eastern Cooperative Oncology Group Phase III clinical trial E4A03, for multiple myeloma, showing significantly better overall survival with lenalidomide plus low-dose dexamethasone therapy compared to lenalidomide plus high-dose dexamethasone, were reported today by S. Vincent Rajkumar, M.D. at the American Society of Hematology's annual meeting.

Currently lenalidomide and high-dose dexamethasone, referred to as Rev/Dex, is used as second-line treatment for myeloma. This same treatment has been used off-label (not currently approved by the U.S. Food and Drug Administration (FDA) for this particular use) by physicians for their newly-diagnosed patients, with overall response rates and one-year survival rates in the 90 percent range.

"The standard treatment for myeloma usually includes high doses of steroids such as dexamethasone. In this study we were hoping to find that a lower dose of steroids would be just as effective," says Dr. Rajkumar, Mayo Clinic Cancer Center hematologist and lead investigator of the study. "We were surprised to find that the regimen with high-dose steroids actually was decreasing survival, besides contributing to increased side effects."

The study compared combination treatment of oral medications lenalidomide (a novel chemotherapeutic agent) and either high- or low-dose dexamethasone (a potent steroid effective against myeloma) in 445 patients with newly diagnosed myeloma. Lenalidomide plus high-dose dexamethasone had an 18-month survival rate of 80 percent. The comparative therapy using low-dose dexamethasone showed a significantly higher 91 percent overall survival rate at 18 months, with much less toxicity.

"The lower survival rates with the high-dose dexamethasone can be attributed to disease progression as well as treatment-related toxicities," says Dr. Rajkumar. "This is a major advance in the treatment of this cancer, and also gives researchers a new direction to explore — that more is not necessarily better."

All patients on the high-dose dexamethasone arm of the clinical trial were moved to the low-dose arm in April 2007, following an early closure announcement.

Mayo Clinic's Rafael Fonseca, M.D., and Philip Greipp, M.D., assisted in the research. Other researchers contributing to the study included Susanna Jacobus, Dana Farber Cancer Institute, Boston; Natalie Callander, M.D., University of Wisconsin, Madison; David Vesole, M.D., Ph.D., St. Vincents Hospital, New York; Michael Williams, M.D., University of Virginia, Charlottesville; Rafat Abonour, M.D., Indiana University, Indianapolis; and David Siegel, M.D., Ph.D.; Hackensack University Medical Center, New Jersey.

For more information on hematology research at Mayo Clinic Cancer Center, visit the Web site.

Multiple Myeloma
Multiple myeloma, also called myeloma, is an incurable plasma cell (white blood cells in bone marrow) cancer, for which the cause is unknown. The American Cancer Society reports that nearly 20,000 people will have been diagnosed with myeloma by the end of 2007. Myeloma interferes with bone marrow function and the immune system, and can cause bones to erode, anemia, infection and possibly kidney failure.

Off-Label Prescriptions
Off-label use of medication is not unusual in medical practice, and is allowed by FDA regulation. Clinical trials are conducted for drugs on a specific disease with very narrow criteria (for example newly-diagnosed or recurrent cancer, but not both). When experienced physicians understand the effects of different medications, they are able to administer them in similar situations that may not have been included in the original drug studies — for effective results. Because clinical trials are required for each additional use of a drug, sometimes taking years to result in a label change, off-label use has become common.

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